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Reversible redox energy coupling in electron transfer chains

Abstract

Reversibility is a common theme in respiratory and photosynthetic systems that couple electron transfer with a transmembrane proton gradient driving ATP production. This includes the intensely studied cytochrome bc1, which catalyses electron transfer between quinone and cytochrome c. To understand how efficient reversible energy coupling works, here we have progressively inactivated individual cofactors comprising cytochrome bc1. We have resolved millisecond reversibility in all electron-tunnelling steps and coupled proton exchanges, including charge-separating hydroquinone–quinone catalysis at the Qo site, which shows that redox equilibria are relevant on a catalytic timescale. Such rapid reversibility renders popular models based on a semiquinone in Qo site catalysis prone to short-circuit failure. Two mechanisms allow reversible function and safely relegate short-circuits to long-distance electron tunnelling on a timescale of seconds: conformational gating of semiquinone for both forward and reverse electron transfer, or concerted two-electron quinone redox chemistry that avoids the semiquinone intermediate altogether.

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Figure 1: Cofactors and their energetics in R. capsulatus.
Figure 2: Flash-activated haem b reduction.
Figure 3: Extent of flash-activated Qo site catalysis fitted to the simple equilibrium model.
Figure 4: Intermonomer tunnelling in cytochrome bc1.
Figure 5: Rates of Qi-inhibited haem b reduction and reoxidation in cofactor knockouts as a function of pH.
Figure 6: Qo site catalysis and short-circuits in physiologically reversible cytochrome bc1.

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Acknowledgements

This work was supported by grants from the National Institutes of Health to P.L.D. and F.D.

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Osyczka, A., Moser, C., Daldal, F. et al. Reversible redox energy coupling in electron transfer chains. Nature 427, 607–612 (2004). https://doi.org/10.1038/nature02242

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